Antiplaque, antigingivitis, anticaries oral composition

ABSTRACT

Oral composition containing an effective amount of N-methylpyrrolidone alone or in combination with a noncationic antibacterial agent such as Triclosan for topical application for the prevention of plaque, gingivitis and/or caries.

This application is a continuation-in-part of prior co-pendingapplication Ser. No. 07/992,416 filed Dec. 16, 1992, now abandoned.

FIELD OF THE INVENTION

The present invention relates to an antiplaque, antigingivitis,anticaries oral composition. More particularly, the present inventionrelates to an oral composition containing N-methylpyrrolidone ##STR1##alone or in combination with a noncationic antibacterial compound.

BACKGROUND OF THE INVENTION.

Oral compositions which inhibit calculus formation on dental surfacesare highly desirable since calculus is one of the causative factors inperiodontal conditions. The reduction of calculus, therefore, promotesoral hygiene. Polyphosphates, such as tetraalkali metal pyrophosphates,are examples of anticalculus agents.

Dental plaque is a precursor of calculus. Unlike calculus, however,plaque may form on any part of the tooth surface, particularly at thegingival margin. Hence, besides being unsightly, it is implicated in theoccurrence of gingivitis.

Accordingly, it is desirable to include effective antiplaque agents inoral compositions, optionally in combination with an anticalculus agent.Antiplaque agents found particularly effective are noncationicantibacterial agents, such as halogenated diphenyl ethers, especiallyTriclosan (2',4',4'-2-trichloro-2-hydroxydiphenyl ether), as disclosedin Gaffar et al., U.S. Pat. No 5,037,637, incorporated herein byreference. However, since halogenated diphenyl ethers and othernoncationic antibacterial agents are not readily soluble in water,alternate solvents are desirable to optimize their effectiveness.

Pyrrolidone compounds, other than N-methylpyrrolidone, have previouslybeen employed for a variety of purposes in oral compositions. Forexample, Roberts et al., U.S. Reissue Pat. No. 29,634 discloses the useof polyvinyl pyrrolidone (PVP) as a binder to form a polishing agentinto agglomerated particles. PVP is disclosed as a viscosity adjuster inPrussin, U.S. Pat. No. 3,954,962, as a gelling agent in Norfleet, U.S.Pat. No. 3,840,657, a cooling agent in Humbert et al., U.S. Pat. No.3,917,613, and a synthetic gum in Aguilar U.S. Pat. No. 4,344,931. PVPis further disclosed for uses in other oral compositions with hydrogenperoxide. Both Simon et al, U.S. Pat. Nos. 4,521,403 and 4,567,036 teachto the use of PVP with hydrogen peroxide in controlling disease of theteeth and periodontum. Merianos et al, U.S. Pat. No. 5,130,124 teachesto the use of PVP as a film forming antimicrobial composition whencombined with hydrogen peroxide.

Pyrrolidone compounds have also been incorporated into dentifricecompositions to kill bacteria and/or retard the formation of plaque andtartar. Ploger et al., U.S. Pat. No. 3,960,888, disclosepyrrolidone-5,5-diphosphonic acids as antitartar and antiplaque agents.Murdrak, U.S. Pat. No. 2,757, 125, discloses N-higheralkyl-4-carboxy-2-pyrrolidones as antibacterial agents for oralcompositions. Login et al., U.S. Pat. Nos. 4,732,990; 4,830,850; and4,837,013 disclose quaternized nitrogen compounds including derivativesof pyrrolidone as antibacterial agents for dentifrice compositionsand/or mouthwashes.

Substituted pyrrolidone compounds have been used to retard plaqueformation as disclosed in Blackburne et al, U.S. Pat. No. 4,093,711;Shapiro et al., U.S. Pat. Nos. 4,117,107 and 4,117,108; and Hollister,U.S. Pat. No. 4,621,120.

Dunn et al, U.S. Pat. No. 4,975,271, teaches to use N-methylpyrrolidoneas one of several skin penetration enhancer solvents for a drug orbioactive agent which is applied directly to oral mucosa. Dentalsurfaces are not contacted. Mouthrinses and other topically applied oralmedicinal agents which would contact dental surfaces as well as oralmucosa are specifically excluded.

It would be desirable to enhance the solubility of noncationicantibacterial agents to improve their effectiveness. It would also bedesirable to provide an oral composition containing an antiplaque agentwith enhanced antiplaque effectiveness.

SUMMARY OF THE INVENTION

In accordance with the present invention N-methylpyrrolidone[1-methyl-2-pyrrolidone (1)] has been found to have a potent antiplaqueeffect when employed in an oral composition alone and to enhance theeffect of noncationic antibacterial agents such as halogenated diphenylethers, particularly Triclosan in the prevention of plaque, gingivitisand caries.

The present invention is directed to an oral composition comprising anorally acceptable vehicle suitable for topically contacting dentalsurfaces and gums and up to about 20% by weight N-methylpyrrolidone asan antiplaque agent in the presence or absence of an antibacterialagent, preferably a substantially water-insoluble noncationicantibacterial agent.

The amount of N-methylpyrrolidone in this invention is typically about0.5 to 20% by weight based on the total weight of the dental compositionand preferably about 1 to 15% and most preferably about 5 to 10%. Gumirritation can be avoided when N-methylpyrrolidone is used in amounts ofup to about 20% by weight of the topically applied oral composition.

A further aspect of the invention is a method for reducing plaqueformation comprising topically contacting dental surfaces and gums withan oral composition comprising a liquid vehicle suitable for topicallycontacting dental surfaces and gums and as an antiplaque agent, up toabout 20% N-methylpyrrolidone based on the total weight of thecomposition. Preferably, the composition is contacted with dentalsurfaces and gums about 1 to 3 times a day.

The composition and process may include one or more antibacterial agentswhich are particularly desirable from consideration of antiplaqueeffectiveness, safety and formulation.

DETAILED DESCRIPTION OF THE INVENTION

The following antibacterial agents may be incorporated into the oralcomposition of the present invention:

    ______________________________________                                        HALOGENATED DIPHENYL ETHERS                                                   2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triciosan)                        2,2'-dihydroxy-5,5'-dibromo-diphenyl ether                                    PHENOLIC COMPOUNDS                                                            (including phenol and its homologs, mono- and poly-alkyl                      and aromatic halophenols, resorcinol and its derivatives                      and bisphenolic compounds and                                                 PHENOL AND ITS HOMOLOGS                                                       PHENOL                                                                        2 Methyl                                                                      Phenol                                                                        3 Methyl                                                                      Phenol                                                                        4 Methyl                                                                      Phenol                                                                        4 Ethyl                                                                       Phenol                                                                        2,4-Dimethyl                                                                  Phenol                                                                        2,5-Dimethyl                                                                  Phenol                                                                        3,4-Dimethyl                                                                  Phenol                                                                        2,6-Dimethyl                                                                  Phenol                                                                        4-n-Butyl                                                                     Phenol                                                                        4-n-Amyl                                                                      Phenol                                                                        4-tert-Amyl                                                                   Phenol                                                                        4-n-Hexyl                                                                     Phenol                                                                        4-n-Heptyl                                                                    Phenol                                                                        MONO- AND POLY-ALKYL AND                                                      AROMATIC HALOPHENOLS                                                          Methyl                                                                        p-Chlorophenol                                                                Ethyl                                                                         p-Chlorophenol                                                                n-Propyl                                                                      p-Chlorophenol                                                                n-Butyl                                                                       p-Chlorophenol                                                                n-Amyl                                                                        p-Chlorophenol                                                                sec.-Amyl                                                                     p-Chlorophenol                                                                n-Hexyl                                                                       p-Chlorophenol                                                                Cyclohexyl                                                                    p-Chlorophenol                                                                n-Heptyl                                                                      p-Chlorophenol                                                                n-Octyl                                                                       p-Chlorophenol                                                                O-CHLOROPHENOL                                                                Methyl                                                                        o-Chlorophenol                                                                Ethyl                                                                         o-Chlorophenol                                                                n-Propyl                                                                      o-Chlorophenol                                                                n-Butyl                                                                       o-Chlorophenol                                                                n-Amyl                                                                        o-Chlorophenol                                                                tert-Amyl                                                                     o-Chlorophenol                                                                n-Hexyl                                                                       o-Chlorophenol                                                                n-Heptyl                                                                      o-Chlorophenol                                                                p-CHLOROPHENOL                                                                o-Benzyl                                                                      p-Chlorophenol                                                                o-Benzyl-m-methyl                                                             p-Chlorophenol                                                                o-Benzyl-m, m-dimethyl                                                        p-Chlorophenol                                                                o-Phenylethyl                                                                 p-Chlorophenol                                                                o-Phenylethyl-m-methyl                                                        p-Chlorophenol                                                                3-Methyl                                                                      p-Chlorophenol                                                                3,5-Dimethyl                                                                  p-Chlorophenol                                                                6-Ethyl-3-methyl                                                              p-Chlorophenol                                                                6-n-Propyl-3-methyl                                                           p-Chlorophenol                                                                2-iso-Propyl-3-methyl                                                         p-Chlorophenol                                                                2-Ethyl-3,5-dimethyl                                                          p-Chlorophenol                                                                6-sec. Butyl-3-methyl                                                         p-Chlorophenol                                                                2-iso-Propyl-3,5-dimethyl                                                     p-Chlorophenol                                                                6-Diethylmethyl-3-methyl                                                      p-Chlorophenol                                                                6-iso-Propyl-2-ethyl-3-methyl                                                 p-Chlorophenol                                                                2-sec. Amyl-3,5-dimethyl                                                      p-Chlorophenol                                                                2-Diethylmethyl-3,5-dimethyl                                                  p-Chlorophenol                                                                6-sec. Octyl-3-methyl                                                         p-Chlorophenol                                                                p-BROMOPHENOL                                                                 Methyl                                                                        p-Bromophenol                                                                 Ethyl                                                                         p-Bromophenol                                                                 n-Propyl                                                                      p-Bromophenol                                                                 n-Butyl                                                                       p-Bromophenol                                                                 n-Amyl                                                                        p-Bromophenol                                                                 sec-Amyl                                                                      p-Bromophenol                                                                 n-Hexyl                                                                       p-Bromophenol                                                                 cyclohexyl                                                                    p-Bromophenol                                                                 o-BROMOPHENOL                                                                 tert.-Amyl                                                                    o-Bromophenol                                                                 n-Hexyl                                                                       o-Bromophenol                                                                 n-Propyl-m,m-Dimethyl                                                         o-Bromophenol                                                                 2-Phenyl Phenol                                                               4-chloro-2-methyl phenol                                                      4-chloro-3-methyl phenol                                                      4-chloro-3,5-dimethyl phenol                                                  2,4-dichloro-3,5-dimethyl phenol                                              3,4,5,6-terabromo-2-methyl phenol                                             5-methyl-2-pentylphenol                                                       4-isopropyl-3-methylphenol                                                    5-chloro-2-hydroxydiphenylmethane                                             RESORCINOL AND ITS DERIVATIVES                                                RESORCINOL                                                                    Methyl                                                                        Resorcinol                                                                    Ethyl                                                                         Resorcinol                                                                    n-propyl                                                                      Resorcinol                                                                    n-Butyl                                                                       Resorcinol                                                                    n-Amyl                                                                        Resorcinol                                                                    n-Hexyl                                                                       Resorcinol                                                                    n-Heptyl                                                                      Resorcinol                                                                    n-Octyl                                                                       Resorcinol                                                                    n-Nomyl                                                                       Resorcinol                                                                    Phenyl                                                                        Resorcinol                                                                    Benzyl                                                                        Resorcinol                                                                    Phenylethyl                                                                   Resorcinol                                                                    Phenylpropyl                                                                  Resorcinol                                                                    p-Chlorobenzyl                                                                Resorcinol                                                                    5-Chloro                                                                      2,4-Dihydroxydiphenyl Methane                                                 4'-Chloro                                                                     2,4-Dihydroxydiphenyl Methane                                                 5-Bromo                                                                       2,4-Dihydroxydiphenyl Methane                                                 4'-Bromo                                                                      2,4-Dihydroxydiphenyl Methane                                                 BISPHENOLIC COMPOUNDS                                                         2,2'-methylene bis (4-chlorophenol)                                           2,2'-methylene bis (3,4,6-trichlorophenol)                                    2,2'-methylene bis (4-chloro-6-bromophenol)                                   bis (2-hydroxy-3,5-dichlorophenyl) sulfide                                    bis (2-hydroxy-5-chlorobenzyl) sulfide                                        HALOGENATED CARBANILIDES                                                      3,4,4'-trichlorocarbanilide                                                   3-trifluoromethyl-4,4'-dichlorocarbanilide                                    3,3',4-trichlorocarbanilide                                                   ______________________________________                                    

The antibacterial agent, when employed, is present in the oralcomposition in an effective antiplaque amount, typically about 0.01 to5% by weight, preferably about 0.03 to 1% by weight. The antibacterialagent is substantially water-insoluble, meaning that its solubility isless than about 1% by weight in water at 25° C. and may be even lessthan about 0.01% by weight. The solubility of the antibacterial agent isincreased by the addition of an effective amount of n-methylpyrrolidone.As a consequence, a greater amount of the antibacterial agent isdelivered to the teeth where plaque is likely to develop.

The preferred halogenated diphenyl ether is Triclosan. The preferredphenolic compounds are n-hexyl resorcinol and 2,2'-methylene bis(4-chloro-6-bromophenol). The most preferred antibacterial antiplaquecompound is Triclosan. Triciosan is described in more detail in Gaffaret al., U.S. Pat. No. 5,037,637, and references cited therein, each ofwhich is incorporated herein by reference.

Cationic antibacterial agents-may optionally be employed in thecompositions of the present invention. Such agents are disclosed in, forexample, Gaffar, U.S. Pat. No. 4,339,430, incorporated herein byreference, and include antibacterial quaternary ammonium compounds suchas benzethonium chloride and dissobutylphenoxyethoxyethyl dimethylbenzyl ammonium chloride.

Other antibacterial antiplaque quaternary ammonium compounds includethose in which one or two of the substituents on the quaternary nitrogenhas a carbon chain length (typically an alkyl group) of some 8 to 20,typically 10 to 18, carbon atoms while the remaining substituents have alower number of carbon atoms (typically alkyl or benzyl group), such as1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethylammonium bromide, dodecyl dimethyl (2-phenoxyethyl) ammonium bromide,benzyl dimethyl stearyl ammonium chloride, cetylpyridinium chloride andquaternized 5-amino-1,3-bis (2-ethyl-hexyl)-5-methyl hexahydropyrimidine are exemplary of other typical quaternary ammoniumantibacterial agents.

Other types of cationic antibacterial agents which are desirablyincorporated in the present composition include the amidines such assubstituted guanidines e.g. chlorhexidine and the correspondingcompound, alexidine, having 2-ethylhexyl groups instead of chlorophenylgroups, as well as other known bis-biguanides.

Cationic tertiary amines may also be used and include those having onefatty alkyl group (typically 12 to 18 carbon atoms) and 2poly(oxyethylene) groups attached to the nitrogen (typically containinga total of from 2 to 50 ethenoxy groups per molecule) and salts thereofwith acids and compounds of the structure: ##STR2## where R is a fattyalkyl group containing 12 to 18 carbon atoms and x, y, and z total 3 orhigher, as well as salts thereof.

Cationic antibacterial agents which may be employed in the practice ofthis invention are typically employed in amounts such that the oralproduct contains about 0.001 to 15% by weight of the agent, preferablyabout 0.01 to 5% by weight, and most preferably about 0.25 to 1.0% byweight referring to its free base form, based on the total weight of theoral composition.

Other cationic antibacterial agents for use in the present invention aredescribed in Gaffar, U.S. Pat. No. 4,339,430, and references mentionedtherein.

The present oral composition preferably contains an anticalculus agent.The preferred anticalculus agents are linear molecularly dehydratedpolyphosphate salts which are well known, being generally employed inthe form of their wholly or partially neutralized water-soluble alkalimetal (e.g. potassium and preferably sodium) or ammonium salts, and anymixtures thereof. Representative examples include sodiumhexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodiummonoacid and tetrasodium pyrophosphates and the like. The anticalculusagents are generally employed in the instant oral compositions inapproximate amounts of about 0.1 to 7% by weight, more preferably about2 to 7% by weight.

Particularly desirable anticalculus agents of the polyphosphate type aretetraalkali metal pyrophosphates, including mixtures thereof, such astetrasodium pyrophosphate, tetrapotassium pyrophosphate and mixturesthereof. An anticalculus agent comprising about 4.3% to 7% by weight ofthe oral compositions wherein the weight ratio of tetrapotassiumpyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 toabout 6:1 is especially preferred.

In order to optimize the effectiveness of the oral composition, if oneor more polyphosphate compounds are present, inhibitors againstenzymatic hydrolysis of the polyphosphate are desirably present. Suchinhibitors include a fluoride ion source and/or synthetic anionicpolymeric polycarboxylates.

The sources of fluoride ions, or fluorine-providing component, as theacid phosphatase and pyrophosphatase enzyme inhibitor component, arewell known in the art as anti-caries agents. These compounds may beslightly soluble in water or may be fully water-soluble. They arecharacterized by their ability to release fluoride ions in water, bytheir freedom from undesired reaction with other compounds of the oralpreparation and by their anticaries and enzyme inhibitory activity.Among these materials are inorganic fluoride salts, such as solublealkali metal, alkaline earth metal salts, for example, sodium fluoride,potassium fluoride, ammonium fluoride, calcium fluoride, a copperfluoride such as cuprous fluoride, zinc fluoride, barium fluoride,sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate,sodium monofluorophosphate, aluminum mono- and di-fluorophosphate, andfluorinated sodium calcium pyrophosphate. Alkali metal and tinfluorides, such as sodium and stannous fluorides, sodiummonofluorophosphate (MFP) and mixtures thereof, are preferred.

The amount of fluorine-providing compound is dependent to some extentupon the type of compound, its solubility, and the type or oralpreparation, but it must be a non-toxic amount, generally about 0.005 toabout 3.0% in the preparation. In a dentifrice preparation, e.g. dentalgel, toothpaste (including cream), tooth powder, or dental tablet, anamount of such compound which releases up to about 5,000 ppm of fluorideion by weight of the preparation is considered satisfactory. Anysuitable minimum amount of such compound may be used, but it ispreferable to employ sufficient compound to release about 300 to 2,000ppm, more preferably about 800 to about 1,500 ppm of fluoride ion.

Typically, in the cases of alkali metal fluorides, this component ispresent in an amount up to about 2% by weight, based on the weight ofthe preparation, and preferably in the range of about 0.05% to 1%. Inthe case of sodium monofluorophosphate, the compound may be present inan amount of about 0.1 to 3%, more typically about 0.76%.

In dentifrice preparations such as lozenges and chewing gum, thefluorine-providing compound is typically present in an amount sufficientto release up to about 500 ppm, preferably about 25 to 300 ppm by weightof fluoride ion. Generally about 0.005 to 1.0% by weight of suchcompound is present.

Synthetic anionic polymeric polycarboxylates useful as enzymeinhibitors, particularly to inhibit alkaline phosphatase, mayadditionally enhance the antibacterial effect of the substantiallywater-insoluble noncationic antibacterial agents such as Triclosan.Examples of these agents are disclosed in Shedlovsky U.S. Pat. No.3,429,963, Dichter et al. U.S. Pat. No. 3,956,480, Gaffar U.S. Pat. Nos.4,138,477 and 4,152,420, and Gaffar et al. U.S. Pat. No. 4,183,914, eachincorporated herein by reference.

The synthetic anionic polymeric polycarboxylates optionally butpreferably employed herein are, as indicated above, well known, beingoften employed in the form of their free acids or preferably partiallyor more preferably fully neutralized water-soluble alkali metal (e.g.potassium and preferably sodium) or ammonium salts. Preferred are 1:4 to4:1 copolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether (maleicanhydride) having a molecular weight (M.W.) of about 30,000 to1,000,000. These copolymers are available for example as Gantrez AN 139(M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97 PharmaceuticalGrade of GAF Corporation. The term "synthetic" is intended to excludeknown thickening or gelling agents comprising carboxymethylcellulose andother derivatives of cellulose and natural gums.

Other operative polymeric polycarboxylates include those disclosed inDichter et al., U.S. Pat. No. 3,956,480, referred to above, such as the1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethylmethacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter beingavailable for example as Monsanto EMA No. 1103, M.W. 10,000 and EMAGrade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethylmethacrylate, methyl or ethyl acrylate, isobutyl vinyl ether orN-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred to Gaffar, U.S. Pat. No. 4,138,477, and Gaffar et al., U.S.Pat. No. 4,183,914, include copolymers of maleic anhydride with styrene,isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic andpolymaleic acids, and sulfoacrylic oligomers of M.W. as low as 1,000,available as Uniroyal ND-2.

Suitable generally are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrilacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility.

Also useful herein are so-called carboxyvinyl polymers disclosed astoothpaste components in Chown et al. U.S. Pat. No. 3,980,767; Robertset al. U.S. Pat. No. 3,935,306; Perla et al. U.S. Pat. No. 3,919,409;Harrison U.S. Pat. No. 3,911,104, and Colodney et al. U.S. Pat. No.3,711,604. They are commercially available for example under thetrademarks Carbopol 934, 940 and 941 of B. F. Goodrich, these productsconsisting essentially of a colloidally water-soluble polymer ofpolyacrylic acid cross-linked with from about 0.75% to 2.0% by weight ofpolyallyl sucrose or polyallyl pentaerythritol as cross- linking agent.

The synthetic anionic polymeric polycarboxylate component is mainly ahydrocarbon with optional halogen and 0-containing substituents andlinkages as present in for example ester, ether and OH groups, and whenpresent is generally employed in the instant compositions in approximateweight amounts of about 0.05 to 3% by weight, preferably about 0.05 to2% by weight, more typically employed in dentifrice compositionstypically containing a dental abrasive and used in conjunction withbrushing of the teeth, e.g. tooth pastes (including creams), gels,powders and tablets. Amounts in excess of these ranges may be employedfor thickening or gelling purposes. The preferred synthetic anionicpolymeric carboxylates (e.g. Gantrez) also enhance the antibacterialeffect of the antiplaque agent. Other antibacterial-enhancing agents mayalso be used.

Antibacterial-enhancing agents (AEAs), when present, enhance delivery ofthe water-insoluble noncationic antibacterial agent to, and retentionthereof on, oral surfaces, in accordance with a preferred embodiment ofthe present invention. AEAs are employed in amounts effective to achievesuch enhancement preferably within the range in the oral composition ofabout 0.005% to 4%, preferably about 0.1% to 3%, more preferably about0.5% to 2.5% by weight.

The AEA may be a simple compound, preferably a polymerizable monomer,more preferably a polymer, which latter term is entirely generic,including for example oligomers, homopolymers, copolymers of two or moremonomers, ionomers, block copolymers, graff copolymers, cross-linkedpolymers and copolymers, and the like. The AEA may be natural orsynthetic, and water-insoluble or preferably water (saliva) soluble orswellable (hydratable, hydrogel forming). It preferably has a (weight)average molecular weight of about 100 to 1,000,,000, preferably about1,000 to 1,000,000, more preferably about 2,000 or 2,500 to 250,000 or500,000.

The AEA ordinarily contains at least one delivery-enhancing group, whichis preferably acidic such as sulfonic, phosphonic, or more preferablyphosphonic or carboxylic, or salt thereof, e.g. alkali metal orammonium, and at least one organic retention-enhancing group, preferablya plurality of both the delivey-enhancing and retention-enhancinggroups, which latter groups preferably have the formula - (X)_(n) --Rwherein X is O, N, S, SO, SO₂, P, PO or Si or the like, R is hydrophobicalkyl, alkenyl, acyl, aryl, alkaryl, araikyl, heterocyclic or theirinert-substituted derivatives and n is zero or 1 or more. The aforesaid"inert-substituted derivatives" are intended to include substituents onR which are generally nonhydrophilic and do not significantly interferewith the desired functions of the AEA as enhancing the delivery of theantibacterial agent to, and retention thereof on, oral surfaces such ashalo, e.g. CI, Br, I, and carbo and the like. Illustrations of suchretention-enhancing groups listed in Table 1.

                  TABLE 1                                                         ______________________________________                                        n   X      --(X).sub.n R                                                      ______________________________________                                        0   --     methyl, ethyl, propyl, butyl, isobutyl, t-butyl                               cyclohexyl, allyl, benzyl, phenyl, chlorophenyl,                              xylyl, pryridyl, furanyl, acetyl, benzoyl, butyryl,                           terephthaloyl, etc.                                                1   O      ethoxy, benzyloxy, thioacetoxy, phenoxy,                                      carboethoxy, carbobenzyloxy, etc.                                      N      ethylamino, diethylamino, propylamido, benzylamino,                           benzoylamido, phenylacetamido, etc.                                    S      thiobutyl, thioisobutyl, thioallyl, thiobenzyl,                               thiophenyl, thiopropionyl, phenylthioacetyl,                                  thiobenzoyl, etc.                                                      SO     butylsulfoxy, allylsulfoxy, benzylsulfoxy,                                    phenylsulfoxy, etc.                                                    SO.sub.2                                                                             butylsulfonyl, allylsulfonyl, benzylsulfonyl,                                 phenylsulfonyl, etc.                                                   P      diethylphosphinyl, ethylvinylphosphinyl,                                      ethylallylphosphinyl, ethylbenzylphosphinyl,                                  ethylphenylphosphinyl, etc.                                            PO     diethylphosphinoxy, ethylvinylphosphinoxy,                                    methylallylphosphinoxy, methylbenzylphosphinoxy,                              methylphenylphosphinoxy, etc.                                          Si     trimethylsilyl, dimethylbutylsilyl,                                           dimethylbenzylsilyl, dimethylvinylsilyl,                                      dimethylallylsilyl, etc.                                           ______________________________________                                    

As employed herein, the delivery-enhancing group refers to one whichattaches or substantively, adhesively, cohesively or otherwise bonds theAEA (carrying the antibacterial agent) to oral (e.g. tooth and gum)surfaces, thereby "delivering" the antibacterial agent to such surfaces.The organic retention-enhancing group, generally hydrophobic, attachesor otherwise bonds the antibacterial agent to the AEA, thereby promotingretention of the antibacterial agent to the AEA and indirectly on theoral surfaces. In some instances, attachment of the antibacterial agentoccurs through physical entrapment thereof by the AEA, especially whenthe AEA is a cross-linked polymer, the structure of which inherentlyprovides increased sites for such entrapment. The presence of a highermolecular weight, more hydrophobic cross-linking moiety in thecross-linked polymer still further promotes the physical entrapment ofthe antibacterial agent to or by the cross-linked AEA polymer.

Preferably, the AEA is a anionic polymer comprising a chain or backbonecontaining repeating units each preferably containing at least onecarbon atom and preferably at least one directly or indirectly pendent,monovalent delivery-enhancing group and at least one directly orindirectly pendent monovalent retention-enhancing group geminally,vicinally or less preferably otherwise bonded to atoms, preferablycarbon, in the chain. Less preferably, the polymer may containdelivery-enhancing groups and/or retention-enhancing groups and/or otherdivalent atoms or groups as links in the polymer chain instead of or inaddition to carbon atoms, or as cross-linking moieties.

It will be understood that any examples or illustrations of AEAsdisclosed herein which do not contain both delivery-enhancing groups andretention enhancing groups may and preferably should be chemicallymodified in known manner to obtain the preferred AEAs containing bothsuch groups and preferably a plurality of each such groups. In the caseof the preferred polymeric AEAs, it is desirable, for maximizingsubstantivity and delivery of the antibacterial agent to oral surfaces,that the repeating units in the polymer chain or backbone containing theacidic delivery-enhancing groups constitute at least about 10%preferably at least about 50%, more preferably at least about 80% up to95% or 100% by weight of the polymer.

According to a preferred embodiment of this invention, the AEA comprisesa polymer containing repeating units in which one or more phosphonicacid delivery-enhancing groups are bonded to one or more carbon atoms inthe polymer chain. An example of such an AEA is poly (vinyl phosphonicacid) containing units of Formula I: ##STR3## which however does notcontain a retention-enhancing group. A group of the latter type wouldhowever be present in poly(1-phosphonopropene) with units of Formula II:##STR4## A preferred phosphonic acid-containing AEA for use herein ispoly (beta styrene phosphonic acid) containing units of Formula III:##STR5## wherein Ph is phenyl, the phosphonic delivery-enhancing groupand the phenyl retention-enhancing group being bonded on vicinal carbonatoms in the chain, or a copolymer of beta styrerie phosphonic acid withvinyl phosphonyl chloride having the units of Formula III alternating Orin random association with units of Formula I above, or poly (alphastyrerie phosphonic acid) containing units of Formula IV: ##STR6## inwhich the delivery-enhancing and retention-enhancing groups aregeminally bonded to the chain.

These styrene phosphonic acid polymers and their copolymers with otherinert ethylenically unsaturated monomers generally have molecularweights in the range of about 2,000 to 30,000, preferably about 2,500 to10,000. Such "inert" monomers do not significantly interfere with theintended function of any copolymer employed as an AEA herein.

Other phosphonic-containing polymers include, for example, phosphonatedethylene having units of the Formula V:

    --[(CH.sub.2).sub.14 CHPO.sub.3 H.sub.2 ].sub.n --

where n may for example be an integer or have a value giving the polymera molecular weight of about 3,000; and sodiumpoly(butene-4,4-diphosphonate) having units of the Formula VI: ##STR7##and poly (allyl bis (phosphonoethyl amine) having units of Formula VII:##STR8## Other phosphonated polymers, for example poly (allyl phosphonoacetate), phosphonated polymethacrylate, etc. and the geminaldiphosphonate polymers disclosed in EP Publication 0321233 may beemployed herein as AEAs, provided of course that they contain or aremodified to contain the above-defined organic retention-enhancinggroups. As previously indicated, the most preferred AEAs are syntheticanionic polymeric carboxylates.

The pH of the dentifrice preparations of this invention is generally inthe range of from about 4.5 to about 10 and typically from about 5.5 to9. The pH is preferably in the range of from about 6 to about 8.0. It isnoteworthy that the compositions of the invention may be applied orallyat said pH ranges without substantially decalcifying or otherwisedamaging dental enamel. The pH can be controlled with acid (e.g. citricacid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (aswith sodium citrate, benzoate, carbonate, or bicarbonate, disodiumhydrogen phosphate, sodium dihydrogen phosphate, etc).

In certain desirable forms of this invention, the dentifrice compositionmay be substantially solid or pasty in character, such as tooth powder,a dental tablet, a tooth paste (cream), or a dental gel. The vehicle ofsuch solid or pasty dentifrice preparations typically contains an orallyor dentally acceptable polishing material for use in conjunction with abrushing of the teeth. Examples of such polishing materials arewater-insoluble sodium metaphosphate, potassium metaphosphate,tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalciumphosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesiumphosphate, calcium carbonate, aluminum silicate, zirconium silicate,silica, bentonite, and mixtures thereof. Other suitable polishingmaterials include the particulate thermosetting resins described in U.S.Pat. No. 4,070,510 such as melamine-, phenolic-, and urea-formaldehydes,and cross-linked polyepoxides and polyesters. Preferred polishingmaterials include silica gel or colloidal silica, and complex amorphousalkali metal alumino-silicates.

When visually clear gels are desired, a polishing agent of colloidalsilica, such as those sold under the trademark SYLOID as Syloid 72 andSyloid 74 or under the trademark SANTOCEL as Santocel 100 and alkalimetal aluminosilicate complexes are particularly useful, since they haverefractive indices close to the refractive indices of gellingagent-liquid (including water and/or humectant) systems commonly used indentifrices.

Many of the so-called "water-insoluble" polishing materials are anionicin character and also include small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any conventional manner.The forms of insoluble sodium metaphosphate known as Madrell's salt andKurrol's salt are further examples of suitable materials. Thesemetaphosphate salts exhibit only a minute solubility in water, andtherefore are commonly referred to as insoluble metaphosphates (IMP).There is present therein a minor amount of soluble phosphate material asimpurities, usually a few percent such as up to 4% by weight. The amountof soluble phosphate material, which is believed to include a solublesodium trimetaphosphate in the case of insoluble metaphosphate, may bereduced or eliminated by washing with water if desired. The insolublealkali metal metaphosphate is typically employed in powder form of aparticle size such that no more than about 1% of the material is largerthan about 37 microns.

The polishing material is generally present in the solid or pastycompositions in concentrations of about 10% to 99% by weight.Preferably, it is present in amounts ranging from about 10% to 75% byweight in toothpaste or gel and from about 70% to 99% by weight in toothpowder or tablet.

In a toothpaste, the topical liquid vehicle may comprise water andhumectant typically in an amount ranging from about 10% to 90% by weightof the preparation. Glycerine, propylene glycol, sorbitol, polypropyleneglycol and/or polyethylene glycol (e.g. 400-600) exemplify suitablehumectants/carriers. Also advantageous are liquid mixtures of water,glycerine and sorbitol. In clear gels where the refractive index is animportant consideration, about 3 to 30% by weight of water, about 0 to80% by weight of glycerine, and about 20 to 80% by weight of sorbitol ispreferably employed.

Toothpastes (creams) and gels typically contain in the topical vehicle anatural or synthetic thickener or gelling agent in proportions of about0.1 to 10, preferably about 0.5 to 5% by weight. A suitable thickener issynthetic hectorite, a synthetic colloidal magnesium alkali metalsilicate complex clay available for example as Laponite (e.g. CP, SP2002, D) marketed by Laporte Industries Limited. Laponite D analysisshows, approximately by weight, 58.00% SiO₂, 25.40% MgO, 3.05% Na₂ O,0.98% Li₂ O, and some water and trace metals. Its true specific gravityis 2.53 and it has an apparent bulk density (g./ml. at 8% moisture) of1.0.

Other suitable thickeners include Irish moss, gum tragacanth, starch,polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g.available as Natrosol), sodium carboxymethyl cellulose, and colloidalsilica such as finely ground Syloid (e.g. 244).

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitably labeled packages.Thus, a toothpaste, cream or gel will usually be in a collapsible tube,typically aluminum, lined lead or plastic, or other squeeze, pump orpressurized dispenser for metering out the contents, having a labeldescribing it, in substance, as a toothpaste, gel or dental cream.

In the aspect of the present invention wherein the oral composition is amouthwash or liquid dentifrice, substantially liquid in character, thetopical vehicle, particularly in a mouthwash, is typically awater-alcohol mixture. Generally, the weight ratio of water to alcoholis in the range of from about 1:1 to 20:1, preferably about 3:1 to 10:1and more preferably about 4:1 to 6:1. The total amount of thewater-alcohol mixture in this type of preparation is typically in therange of from about 70 to 99.9% by weight. The alcohol is a non-toxicalcohol such as ethanol or isopropanol, most preferably ethanol. Thealcohol is believed to assist in dissolving water-insoluble noncationicantibacterial agents. Flavoring oil is also believed to perform the samefunction. Humectant such as glycerine and sorbitol may be present in anamount of about 10 to 30% by weight. Liquid dentifrices typicallycontain about 50 to 85% of water, may contain about 0.5 to 20% by weightof non-toxic alcohol and may also contain about 10 to 40% by weight ofhumectant such as glycerine and/or sorbitol. Reference here to sorbitolrefers to the material typically available commercially in 70% aqueoussolutions.

As indicated, the noncationic antibacterial agent is substantiallywater-insoluble. However, in the present invention, particularly withthe AEA, such as polycarboxylate, present in the mouthwash or liquiddentifrice, organic surface-active agent, flavoring oil or non-toxicalcohol are believed to aid dissolving the antibacterial agent to assistit to reach soft oral tissue at or near the gums as well as toothsurfaces. Organic surface-active agents and/or flavoring oils may alsoassist dissolving the antibacterial agents as optional ingredients inoral dentifrice compositions.

Organic surface-active agents are used in the compositions of thepresent invention to achieve increased prophylactic action, assist inachieving thorough and complete dispersion of the anticalculus agentthroughout the oral cavity, and render the instant compositions morecosmetically acceptable. The organic surface-active material ispreferably anionic, nonionic or ampholytic in nature, and it ispreferred to employ as the surface-active agent a detersive materialwhich imparts to the composition detersive and foaming properties.Suitable examples of anionic surfactants are water-soluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglyceride of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsuifoacetates, higher fatty acid esters of 1,2 dihydroxy propanesulfonate, and the substantially saturated higher aliphatic acyl amidesof lower aliphatic amino carboxylic acid compounds, such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals and alkoyltaurines, and the like. Examples of the last mentioned amides andtaurates are N-lauroyl sarcosine, and the sodium, potassium andethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosinewhich should be substantially free from soap or similar higher fattyacid material as well as N-methyl-N-cocoyl (or oleoyl or paimitoyl)taurines. The use of these sarcosinate compounds in the oralcompositions of the present invention is particularly advantageous sincethese materials exhibit a prolonged and marked effect in the inhibitionof acid formation in the oral cavity due to carbohydrate breakdown inaddition to exerting some reduction in the solubility of tooth enamel inacid solutions.

Examples of water-soluble nonionic surfactants are condensation productsof ethylene oxide with various reactive hydrogen-containing compoundsreactive therewith having long hydrophobic chains (e.g. aliphatic chainsof about 12 to 20 carbon atoms), which condensation products("ethoxamers") contain hydrophilic polyoxyethylene moleties, such ascondensation products of poly (ethylene oxide) with fatty acids, fattyalcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate)and polypropyleneoxide (e.g. Pluronic materials).

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds, other anticalculus agents, and/or ammoniatedmaterial such as urea, diammonium phosphate, and mixtures thereof. Theseadjuvants, where present, are incorporated in the preparations inamounts which do not substantially adversely affect the properties andcharacteristics desired. Significant amounts of zinc, magnesium andother metal salts and materials, generally soluble, which would complexwith the active components of the instant invention are to be avoided.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, peppermint, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, dextrose, levulose, sorbitol, xylitol, d-tryptophan,dihydrochalcones, sodium cyclamate, perillartine, APM (aspartyl phenylalanine, methyl ester), saccharine and the like. Suitably, flavoring andsweetening agents may together comprise from about 0.1% to 5% by weightor more of the preparation.

In the preferred practice of this invention an oral compositionaccording to this invention such as a dentifrice is preferably appliedas by brushing regularly to dental enamel, such as every second or thirdday or preferably from 1 to 3 times daily, at a pH of about 4.5 to 10,generally about 5.5 to 9, preferably about 6 to 8, for at least 2 weeksup to 8 weeks or more up to lifetime. The dentifrice is typicallyremoved by rinsing with water after each application.

The compositions of this invention can be incorporated in lozenges, orin chewing gum or other products, e.g. by stirring into a warm gum basetopical vehicle or coating the outer surface of a gum base, illustrativeof which may be mentioned jelutone, rubber latex, vinylite resins, etc.,desirably with conventional plasticizers or softeners, sugar or othersweeteners or carbohydrates such as glucose, sorbitol and the like.

The topical vehicle or carrier in a tablet or lozenge is anon-cariogenic solid water-soluble polyhydric alcohol (polyol) such asmannitol, xylitol, sorbitol, malitol, a hydrogenated starch hydrolysate,Lycasin, hydrogenated glucose, hydrogenated disaccharides, andhydrogenated polysaccharides, in an amount of about 90 to 98% by weightof the total composition. Solid salts such as sodium bicarbonate, sodiumchloride, potassium bicarbonate or potassium chloride may totally orpartially replace the polyol carrier.

Tableting lubricants, in minor amounts of about 0.1 to 5% by weight, maybe incorporated into the tablet or lozenge formulation to facilitate thepreparation of both the tablets and lozenges. Suitable lubricantsinclude vegetable oils such as coconut oil, magnesium stearate, aluminumstearate, talc, starch and carbowax.

Lozenge formulations contain about 2% gum as a barrier agent to providea shiny surface as opposed to a tablet which has a smooth finish.Suitable non-cariogenic gums include Kappa carrageenan, carboxymethyicellulose, hydroxyethyl cellulose, Gantrez, and the like.

The lozenge or tablet may optionally be coated with a coating materialsuch as waxes, shellac, carboxymethyl cellulose, polyethylene/maleicanhydride copolymer or Kappa-carrageenan to further increase the time ittakes the tablet or lozenge to dissolve in the mouth. The uncoatedtablet or lozenge is slow dissolving, providing a sustained release rateof active ingredients of about 3 to 5 minutes. Accordingly, the soliddose tablet and lozenge composition of this invention affords arelatively longer time period of contact of the teeth in the oral cavitywith the active ingredients.

The following examples are further illustrative of the nature of thepresent invention, but it is understood that the invention is notlimited thereto. All amounts and proportions referred to herein and inthe appended claims are by weight.

EXAMPLE 1

The efficacy of N-methylpyrrolidone solutions to inhibit bacterialplaque formation in vitro was assessed using the chemostat plaque modelas described in Gaffar et al., Am. J. Dent., Vol. 3, Special Issue p. S7(September 1990). The experimental apparatus includes a chemostat(Bioflo, Model C32), a source of supplementing growth media, a mixingchamber and several flow cells. The flow cells were specificallydesigned to contain an experimental surface (hydroxyapatite disks 12mm×1 mm thick) on which plaque formation was measured.

A mixed continuous culture of five species of oral microorganisms (A,viscosus LY7, S. mutans JBP, S. sanguis 34, V. parvula ATCC 17745, F.nucleatum 10953) was maintained in the chemostat according to conditionsdescribed by Bradshaw et al., "Effects of Carbohydrate Pulses and pH onPopulation Shifts with Oral Microbial Community In Vitro", J. Dent.Res.9:1288-1302 (1989). Modified BM medium diluted five-fold withdistilled water and supplemented with 2.5 g/l hog gastric mucin was usedas the chemostat growth medium. The bacterial effluent from thechemostat (1 ml/minute) was combined with additional sterile modified BMmedia (1 ml/minute) containing 1 mM sucrose in a mixing chamber toachieve a total flow rate of 2 ml/minute. This mixture was thendistributed to 2 flow cells, each with a flow rate of 1 minute using aperistaltic pump. Bacterial plaque formation was measured after 48hours. The flow cells were treated with a solution of 5%N-methylpyrrolidone for 30 seconds, twice daily. A total of fourtreatments were given during the 48 hour experimental period; at 2.5,20, 26.5 and 44 hours after the start of the flow through the cell.After 48 hours the cells were rinsed with distilled water for 15 minutesat a flow rate of 1 ml/minute. The hydroxyapatite disks were thenremoved for analysis. The procedure was repeated except that the 5%N-methylpyrrolidone solution was replaced by deionized distilled wateras a control.

At the completion of each experiment, approximately 5 hours after thelast treatment, the flow cells were rinsed with distilled water for 15minutes at a flow rate of 1 ml/minute. Bacterial plaque formed onhydroxyapatite disks was removed by immersing the disks in 2 ml of 0.1 NNaOH in a shaking water bath at 37° C. for 45 minutes. After removingthe disks, the samples were sonicated to disperse the plaque. Turbidityof the resulting solution was measured at 610 nm in a spectrophotometer.A 0.1 ml sample was assayed for protein quantity using the Pierce BCAassay kit (Pierce Rockford, Ill.) A 1 ml aliquot of the sample was usedfor the determination of DNA according to the method of Labarca et al.,"A Simple, Rapid Sensitive DNA Assay Procedure", Anal. Biochem.,102:344-352 (1980).

Analysis of the plaque film on germanlure prisms was done using themethod of attenuated total reflectance Fourier transform infraredspectroscopy (ATR/FT-IR). At completion of the experiment, the germaniumprisms were air dried in a vertical position prior to analysis. A PerkinElmer (Norwalk, Conn.), Model 1725 FT-Infrared Spectrometer was used forthe ATR/FT-IR measurements. The prisms were scanned from 4000 to 750cm⁻¹ at a scan rate of 0.2 cm⁻¹ and a resolution of cm⁻¹ . The intensitybands (amide 1 and 2 bands) at 1650 and 1548 cm⁻¹, reflecting mainlyprotein content, were used as an estimate of the quantity of bacterialplaque present. The results are shown in Table 2.

                  TABLE 2                                                         ______________________________________                                        Plaque Parameters (% Reduction vs. Placebo)                                                 Hydroxyapatite                                                                Disks                                                                              Protein DNA     Germanium                                                OD.sup.1                                                                           ug/ml   ug/ml   Surface.sup.2                              ______________________________________                                        Water Placebo   --     --      --                                             5% N-methylpyrrolidone                                                                        59.6   28.8    29.7  29.6                                     ______________________________________                                         .sup.1 OD = optical density                                                   .sup.2 measured by ATRFTIR (Attenuated Total ReflectanceFourier Transform     Infrared Spectroscopy)                                                   

As shown in Table 2, twice a day treatment with a 5% solution ofN-methylpyrrolidone results in a substantial reduction in bacterialplaque formed on both hydroxyapatite and germanium surfaces as comparedwith the water control.

EXAMPLES 2-5

Aqueous solutions of N-methylpyrrolidone having the concentrations shownin Table 3 were tested on in vitro plaque formation using the SalivaFlow Cell System.

The Saliva Flow Cell System was operated in the following manner asdescribed in part in Gaffar et al., Amer. J. Dent., Vol.3, SpecialIssue, pp. S9-S10 (September 1990). A 100 ml glass jar of saliva wasprovided with a rubber stopper, pre-perforated with two holes. A portionof a 1 ml Pyrex disposable pipette, inserted into each hole, served asconnectors. Plastic tubing having an internal diameter of 3.17 mm,served as the "vein" of the flow system.

The flow system was set up in an incubator (Precision Model 4) at 37°C., with the flow cells in a vertical position to minimize airentrapment. Two peristaltic pumps (Model P3), supplied with pre-cutsilicone tubing (3.1 mm internal diameter), were used to produce asteady and pulseless flow rate. Pump I was used to draw saliva from thedispenser through the flow cell and then back to the saliva reservoirfor recirculation. Pump II was used to pulse the flow cell. Y-shapedconnectors linked the two pumps. The flow from each pump was alternatelyshut off during recirculation and pulsing.

Whole human saliva, supplemented with 10% TSB (tryptic soy broth), wascirculated through the flow system at a flow rate of 1 ml/minute,corresponding to a shear stress of about 0.32 dynes-cm⁻². Circulationwas performed for up to 72 hours, with TSB-saliva changes every 24hours.

To assess the effect of N-methylpyrrolidone solutions on plaqueformation, at t=15 minutes, the flow cells were initially pulsed withtest samples at a flow rate of 10 ml/minute for 1 minute. Test solutionresiduals were removed by rinsing with the excess saliva, dilutedanother two-fold. TSB-saliva circulation was resumed after rinsing. Flowcells were treated twice within a 24 hour period, with subsequent changeto fresh TSB-saliva every 24 hours. Treatments were continued for 72hours. The procedure was repeated except that the N-methylpyrrolidonesolution was replaced by deionized distilled water as a control.

All treatments and saliva changes were performed without disassemblingthe system or allowing the plates to go dry. Also, unless otherwisestated, the flow rate was 1 ml/minute.

After 72 hours, the pump was stopped and the recirculating system wasdisconnected from the dispenser. The flow cell was rinsed with deionizeddistilled water (single pass through) for 15 minutes to remove looselybound materials. Although the flow rates were the same for thedeposition and rinse phases, the shear stress was slightly lower in therinse phase. The flow system was then disassembled and the test plateswere air dried in a vertical position before analysis.

The results are shown in Table 3.

After drying for about I hour, the plates were analyzed usingATR-infrared spectroscopy and ellipsometry, which gives the chemicalcomposition of the plaque. The relative absorbance at 1540 cm⁻¹ was usedto quantify the proteinaceous materials (bacteria) making up the plaque.

                  TABLE 3                                                         ______________________________________                                                    % REDUCTION VS. WATER                                                           Plaque on       Plaque film                                     N-methylpyrrolidone                                                                         Germanium Surface.sup.1                                                                       Thickness.sup.2                                 ______________________________________                                          0           --              --                                               1%           22.3            ND.sup.3                                         5%           35.1            11.6                                            10%           57.8            45.3                                            20%           76.5            73.9                                            ______________________________________                                         .sup.1 measured by ATRFTIR spectroscopy                                       .sup.2 measured by ellipsometry                                               .sup.3 ND = not determined                                               

As shown in Table 3, N-methylpyrrolidone significantly reduced theamount of plaque on the substrate as compared with water, in aconcentration dependent manner.

EXAMPLE 6

A mouth rinse in accordance with the present invention was preparedhaving the composition shown in Table 4.

                  TABLE 4                                                         ______________________________________                                                          AMOUNT                                                      COMPONENT         (w/w)                                                       ______________________________________                                        Sodium Saccharin  0.03                                                        Glycerine         10.00                                                       Sodium Lauryl Sulfate                                                                           0.25                                                        N-methylpyrrolidone                                                                             10.00                                                       Triclosan         0.03                                                        Flavoring oil     0.22                                                        Water             QS to 100                                                   ______________________________________                                    

The composition was tested for plaque inhibiting effect using the SalivaFlow Cell System described in connection with Examples 2-5. Two controlcompositions were tested in the same manner. The first controlcomposition [Control (1)] was the same as shown in Table 4 except foromitting N-methylpyrrolidone.

The second control composition [Control (2)] was the same as shown inTable 4 except for omitting both N-methylpyrrolidone and Triclosan. Theresults are shown in Table 5.

                  TABLE 5                                                         ______________________________________                                        PERCENT REDUCTION                                                                           PLAQUE ON                                                                     GERMANIUM   PLAQUE FILM                                         COMPOSITION   SURFACE.sup.1                                                                             THICKNESS.sup.2                                     ______________________________________                                        Example 6     59          45                                                  Control (1)   48          35                                                  Control (2)   --          --                                                  ______________________________________                                         .sup.1 measured by ATRFTIR spectroscopy                                       .sup.2 measured by ellipsometry                                          

As shown in Table 5, N-methylpyrrolidone in combination with Triclosanhas a greater plaque inhibiting effect than Triclosan alone or acomposition containing neither N-methyipyrrolidone or Triclosan.

EXAMPLE 7

The effect of N-methylpyrrolidone on caries development was tested inthe following manner. A 30% by weight aqueous solution ofN-methylpyrrolidone (0.1 ml) was used to test rat caries as described inSchmid et al., "Carlostatic Effects of Monofluorophosphate in Solutionsand Dentifrices in Rats", J. Clin. Dent. Vol. No.3 pp. 75-82 (1989). Therat carries assay employed wearling rats exposed over a three weekperiod to a cariogenic challenge induced by a high sucrose diet andinoculation with acidogenic strains of oral bacteria. The rats weretreated daily with the N-methylpyrrolidone solution or deionizeddistilled water as a control and dental caries was evaluated at the endof the three week test period. The results are shown in Table 6.

                  TABLE 6                                                         ______________________________________                                               Mean                     Smooth                                               Plaque Dentinal Fissure Lesions                                                                        Surface                                       Treatment                                                                              Extent.sup.2                                                                           Initial   Advanced  Lesions                                 ______________________________________                                        Water    1.9      12.0      11.2      16.3                                    N-methyl-                                                                              0.3.sup.1                                                                              7.4.sup.1 3.3.sup.1 3.0.sup.1                               pyrrolidone                                                                   ______________________________________                                         .sup.1 Significantly different from Water control (p < 0.05).                 .sup.2 Rated on a scale of 0 to 4 with 0 indicating no plaque formation       and 4 the highest level of plaque formation.                             

The test data indicates that treatment with a 5% N-methylpyrrolidonesolution significantly reduced the amount of plaque formed and thenumber of dental fissures and smooth surface caries as compared with thewater control.

EXAMPLE 8

The following mouth rinse composition was prepared in accordance withthe present invention:

    ______________________________________                                        INGREDIENTS        AMOUNT (w/w)                                               ______________________________________                                        Sodium Saccharin   0.03                                                       Ethanol (95%)      10.00                                                      Propylene Glycol   7.00                                                       Triclosan          0.03                                                       N-methylpyrrolidone                                                                              5.0                                                        Sodium Lauryl Sulfate                                                                            0.25                                                       Tauranol WSHP                                                                 (n-methyl-N-cocoyl taurine)                                                                      0.2                                                        Gantrez S-96       1.92                                                       NaOH (50% soln.)   0.12                                                       Sorbitol           10.00                                                      Flavoring Oil      0.145                                                      Water              QS to 100                                                  ______________________________________                                    

The composition was prepared by combining the propylene glycol andethanol. Triclosan and the flavoring oil were added to theglycol/ethanol mixture to form a first mixture. All of the remainingcomponents of the mouth rinse composition were combined in water to forma second mixture. The first and second mixtures were then combined toform the mouth rinse composition.

EXAMPLE 9

The following dentifrice composition was prepared in accordance with thepresent invention:

    ______________________________________                                        INGREDIENTS      AMOUNT (w/w)                                                 ______________________________________                                        Precipitated silica                                                                            23.00                                                        Carboxymethylcellulose                                                                         1.60                                                         N-methylpyrrolidone                                                                            10.00                                                        Sorbitol (70%)   38.00                                                        Gantrez S-96     2.50                                                         Triclosan        2.50                                                         Sodium lauryl sulfate                                                                          0.30                                                         Sodium saccharine                                                                              0.20                                                         Water            QS to 100                                                    ______________________________________                                    

EXAMPLE 10

The following dentifrice composition was prepared in accordance with thepresent invention:

    ______________________________________                                        INGREDIENTS      AMOUNT (w/w)                                                 ______________________________________                                        Precipitated silica                                                                            23.000                                                       Carboxymethylcellulose                                                                         1.600                                                        N-methylpyrrolidone                                                                            10.000                                                       Sorbitol (70%)   38.000                                                       Gantrez S-96     2.500                                                        Na.sub.4 P.sub.2 O.sub.7                                                                       2.000                                                        Sodium fluoride  0.243                                                        Sodium lauryl sulfate                                                                          1.500                                                        Sodium saccharine                                                                              0.200                                                        Water            QS to 100                                                    ______________________________________                                    

EXAMPLE 11

The following mouth rinse composition was prepared in accordance withthe present invention.

    ______________________________________                                        INGREDIENTS        AMOUNT (w/w)                                               ______________________________________                                        Ethanol            10.00                                                      N-methylpyrrolidone                                                                              5.00                                                       PEG-40 Sorbitan diisostearate                                                                    0.20                                                       Chlorhexidine digluconate                                                                        0.12                                                       Sodium saccharine  0.03                                                       Glycerine          10.00                                                      Flavoring Oil      0.14                                                       Deionized Water    QS to 100                                                  ______________________________________                                    

EXAMPLE 12

The following mouth rinse composition was prepared in accordance withthe present invention.

    ______________________________________                                        INGREDIENTS        AMOUNT (w/w)                                               ______________________________________                                        Ethanol            10.00                                                      N-methylpyrrolidone                                                                              5.00                                                       PEG-40 Sorbitan diisostearate                                                                    0.20                                                       Cetylpyridinium chloride                                                                         0.12                                                       Sodium saccharine  0.03                                                       Glycerine          10.00                                                      Flavoring Oil      0.14                                                       Deionized Water    QS to 100                                                  ______________________________________                                    

This invention has been described with respect to preferred embodimentsand it will be understood that modifications and variations thereofobvious to those skilled in the art are to be included within the spiritand purview of this application and the scope of the appended claims.

What we claim is:
 1. An oral composition comprising a liquid vehiclesuitable for topically contacting dental surfaces and gums and about0.5% to about 20% by weight based on the total weight of the compositionof N-methylpyrrolidone ##STR9## as an essential antiplaque agent.
 2. Anoral composition comprising a liquid vehicle suitable for topicallycontacting dental surfaces and gums and about 1 to 15% by weight ofN-methylpyrrolidone ##STR10## as an essential antiplaque agent.
 3. Theoral composition of claim 2, comprising a liquid vehicle and anantiplaque N-methylpyrrolidone is present in amount of about 5 to 10% byweight.
 4. The oral composition of any one of claims 1-3 furthercomprising a water insoluble noncationic antibacterial agent.
 5. Theoral composition of claim 4 wherein the antibacterial agent is ahalogenated diphenyl ether.
 6. The oral composition of claim 5 whereinthe halogenated diphenyl ether is Triclosan.
 7. The oral composition ofclaim 4 wherein the amount of the noncationic antibacterial agent isabout 0.01 to 5.0% by weight based on the total weight of thecomposition.
 8. The oral composition of claim 6 further comprising anenzyme inhibiting effective amount of a synthetic anionic polymericpolycarboxyiate.
 9. The oral composition of claim 8 wherein thesynthetic anionic polymeric carboxylate is present in an amount of about0.05 to 3% by weight.
 10. An oral composition comprising a liquidmouthrinse vehicle, about 1 to 15% by weight of N-methylpyrrolidone##STR11## as an essential antiplaque agent, about 0.03 to 1% by weightof Triclosan and about 0.05 to 3.0% by weight of a synthetic anionicpolymeric carboxylate.
 11. The oral composition of claim 10 wherein theamount of N-methylpyrrolidone is about 5 to 10% by weight.
 12. A methodfor reducing plaque formation comprising topically contacting dentalsurfaces and gums with an oral composition comprising the liquidmouthrinse suitable for topically contacting dental surfaces and gumsclaimed in claim
 10. 13. The oral composition of claim 6 furthercomprising about 0.005% to 4% of a water-soluble or swellableantibacterial enhancing agent which contains at least onedelivery-enhancing functional group which enhances delivery of saidTriclosan to oral tooth and gum surfaces and at least one organicretention-enhancing group which enhances attachment or bonding of saidTriclosan to oral tooth and gum surfaces.
 14. The oral composition ofclaim 13 wherein said antibacterial enhancing agent is a syntheticanionic polymer carboxylate.